The present invention relates generally to medical devices and in particular aspects to medical products comprised of extracellular matrix materials.
As further background, collagen-containing materials have found wide use in the medical arts, particularly in applications involving tissue replacement, augmentation, and/or repair. Suitable collagenous materials can be provided by collagenous extracellular matrix (ECM) materials. Such ECM materials can be provided, for example, by materials isolated from a suitable tissue source from a warm-blooded vertebrate, e.g., from the submucosal tissue of a mammal. Such isolated submucosal tissue, for example, small intestinal submucosa (SIS), can be processed so as to have bioremodelable properties and promote cellular invasion and ingrowth. Illustratively, sheet-form SIS materials have been used as surgical grafts to provide tissue support in patients, e.g., in hernia repair operations. In some forms, the sheet-form SIS material includes a multilayered configuration to provide strength, reinforcement, and/or other enhancements to the graft.
It is also well known in the medical arts to treat or otherwise modify isolated collagenous materials. For example, such materials can be crosslinked, i.e., covalent crosslinks can be caused or allowed to form within the material (e.g., within and/or between certain components of the material) and/or between the material and another substance or material. Crosslinking can be used to enhance certain mechanical, chemical, biological, and/or other properties of a collagenous ECM material, for example, to increase the strength of the material and/or to decrease the biodegradation rate of the material. Several crosslinking techniques are known in the art including but not limited to photo-crosslinking, chemical crosslinking, and protein crosslinking induced by dehydration or other means.
Commonly used chemical crosslinkers include, for example, aldehydes such as glutaraldehydes, diimides such as carbodiimides, e.g., 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, acyl-azide, sulfo-N-hydroxysuccinamide, and polyepoxide compounds, including for example polyglycidyl ethers such as ethyleneglycol diglycidyl ether. While these and other crosslinking agents may be useful to crosslink collagenous materials, they can cause undesirable consequences as well. For example, exposure to such materials can destroy the remodelable properties of a remodelable collagenous ECM material. Also, crosslinking a collagenous ECM material with glutaraldehyde can lead to the formation of very high molecular weight glutaraldehyde polymers which are difficult to eliminate from the material, and therefore, may be subsequently released into the patient's body after implantation.
There remain needs for improved and/or alternative medical products that are comprised of ECM materials, as well as methods for manufacturing and using these products. The present invention is addressed to those needs.